Calcyon forms a novel ternary complex with dopamine D 1 receptor through PSD-95 protein and plays a role in dopamine receptor internalization

Chang Man Ha, Daehun Park, Jeong Kyu Han, June Ill Jang, Jae-Yong Park, Eun Mi Hwang, Heon Seok, Sunghoe Chang

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Calcyon, once known for interacting directly with the dopamine D 1 receptor (D 1 DR), is implicated in various neuropsychiatric disorders including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. Although its direct interaction with D 1 DR has been shown to be misinterpreted, it still plays important roles in D 1 DR signaling. Here, we found that calcyon interacts with the PSD-95 and subsequently forms a ternary complex with D 1 DR through PSD-95. Calcyon is phosphorylated on Ser-169 by the PKC activator phorbol 12-myristate 13-acetate or by the D 1 DR agonist SKF-81297, and its phosphorylation increases its association with PSD-95 and recruitment to the cell surface. Interestingly, the internalization of D 1 DR at the cell surface was enhanced by phorbol 12-myristate 13-acetate and SKF-81297 in the presence of calcyon, but not in the presence of its S169A phospho-deficient mutant, suggesting that the phosphorylation of calcyon and the internalization of the surface D 1 DR are tightly correlated. Our results suggest that calcyon regulates D 1 DR trafficking by forming a ternary complex with D 1 DR through PSD-95 and thus possibly linking glutamatergic and dopamine receptor signalings. This also raises the possibility that a novel ternary complex could represent a potential therapeutic target for the modulation of related neuropsychiatric disorders.

Original languageEnglish
Pages (from-to)31813-31822
Number of pages10
JournalJournal of Biological Chemistry
Volume287
Issue number38
DOIs
Publication statusPublished - 2012 Sep 14
Externally publishedYes

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Dopamine Receptors
Dopamine
Phosphorylation
Proteins
Acetates
Attention Deficit Disorder with Hyperactivity
Bipolar Disorder
calcyon
Schizophrenia
Modulation
Association reactions

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Calcyon forms a novel ternary complex with dopamine D 1 receptor through PSD-95 protein and plays a role in dopamine receptor internalization . / Ha, Chang Man; Park, Daehun; Han, Jeong Kyu; Jang, June Ill; Park, Jae-Yong; Hwang, Eun Mi; Seok, Heon; Chang, Sunghoe.

In: Journal of Biological Chemistry, Vol. 287, No. 38, 14.09.2012, p. 31813-31822.

Research output: Contribution to journalArticle

Ha, Chang Man ; Park, Daehun ; Han, Jeong Kyu ; Jang, June Ill ; Park, Jae-Yong ; Hwang, Eun Mi ; Seok, Heon ; Chang, Sunghoe. / Calcyon forms a novel ternary complex with dopamine D 1 receptor through PSD-95 protein and plays a role in dopamine receptor internalization In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 38. pp. 31813-31822.
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